MSH6 (MutS homolog 6)

These findings support the value of routine IHC-based MMR testing in CRC patients. However, confirmatory molecular testing (e.g., MSI analysis, BRAF V600E mutation, MLH1 promoter methylation, or germline sequencing) is necessary to differentiate sporadic from Lynch syndrome-associated dMMR cases and to fully guide Lynch syndrome screening and immunotherapy decisions.

This enabled the decision to treat with immunotherapy for recurrence and also conduct family screening. In spite of the absence of colonic tumours, Lynch syndrome should be suspected in young patients with multiple tumours, particularly when supported by a relevant family history.

P2, N=76, Recruiting, Dechang Diao

Additional variants in MSH6 and CTU2 were also identified and may act as potential modifiers of disease susceptibility, consistent with a multigenic contribution to TGCT risk. These findings support a contributory role for the PDE11A locus in TGCT predisposition and underscore the biological relevance of overlapping sense-antisense genomic regions in hereditary cancer studies.

The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype.

The findings underscore the limitations of tumor-only sequencing and current variant interpretation frameworks in admixed populations. Larger studies integrating matched normal DNA, ancestry-informed analyses, functional validation, and broader sequencing strategies could help improve variant interpretation in Latin American populations.

Here, we report a patient with locally advanced Gleason 5 + 5 = 10 prostatic adenocarcinoma harboring MSH2 and MSH6 genomic deletions with ultrahigh TMB (>250 mutations/megabase) in whom pembrolizumab resulted in a striking complete radiographic, pathologic, and molecular response...Similar T cells are also present in diverse cancers and expand exclusively in ICI-responsive patients. These findings inform on the cellular mechanisms by which immunotherapies may mediate profound responses in patients with dMMR solid tumors.

P3, N=170, Active, not recruiting, Sir Run Run Shaw Hospital | Recruiting --> Active, not recruiting | Trial completion date: Aug 2026 --> Dec 2028

Median overall survival was 23 months, reflecting the high mortality burden of mCRC after hepatectomy. Among all molecular markers evaluated, pS6 was the only one independently associated with worse disease-free survival and higher mortality risk, consistent with its role as a surrogate marker of PI3K/AKT/mTORC1 pathway activation, though a direct causal relationship cannot be established from the present data. A significant association between pS6 and FUS positivity suggests a possible convergence of oncogenic pathways warranting further investigation. Postoperative complications were independent predictors of recurrence, and adjuvant chemotherapy was the strongest independent predictor of improved overall survival. Given the retrospective single-center design and limited sample size, these findings are hypothesis-generating and require prospective multicenter validation before clinical application.

Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.

P=N/A, N=150, Recruiting, Centre Hospitalier Universitaire de Nīmes | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Mar 2026